We request funds to purchase a Carl Zeiss LSM880 with Airyscan confocal microscope based on an Axio Observer Z1 inverted body. The main aim is to replace a heavily used 12-year old Zeiss LSM510 Meta, acquired with Vanderbilt funds and integrated into the Vanderbilt Cell Imaging Shared Resource (CISR) in 2003. The LSM880 with Airyscan will be unique at Vanderbilt and crucial to support the ongoing NIH-funded research of 8 Major User and 10 Minor User groups representing 11 departments within Vanderbilt University. These investigators have essential needs for advanced imaging of cellular anatomy and physiology in a wide range of investigations including, neuropathology and glaucoma, neuronal survival, obesity and diabetes, vesicle trafficking and cancer, cardiac arrhythmia, membrane biophysics, epithelial morphogenesis and cancer, and neural crest lineages in the enteric nervous system. We expect that numerous other NIH-funded projects will be well supported by this instrument; particularly those that require live cell and tissue imaging. We chose the LSM880 with Airyscan as the optimal instrument based on three main goals: 1) to improve the capabilities for live cell and tissue imaging, 2) to improve the capabilities for high-resolution imaging of complex, multi-channel fluorescence microscopy and other advanced techniques, and 3) to maintain continuity with a large number of ongoing investigations with essential needs for confocal microscopy. The requested instrument is configured based on the needs of the Major and Minor Users with significant consideration given to optical performance, high-speed image acquisition at the diffraction-limit, while maintaining live cell physiological conditions. The specifications are fundamental to the successful implementation of the advanced confocal imaging described in the Major User projects. The instrument will be located in Medical Research Building III (room 4155 MRBIII), and maintained by the Cell Imaging Shared Resource (CISR). This room is a CISR microscopy facility, maintained exclusively by the CISR, for the benefit of all Vanderbilt investigators. This space is secure and easily accessible to all major users. The expertise and institutional support for this instrument are exceptional. Dr. Wells, Director of the CISR, is a nationally recognized microscopy expert with experience in confocal, multi-photon-excited fluorescence, and other advanced imaging methods. The CISR has a 21-year history of assisting over 300 investigator labs with cutting-edge imaging expertise and cooperative research support. The VUMC has committed $100,000 to support the long-term operation of the instrument.